Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hooved animals, including cattle, swine, sheep, goats, and deer, that rapidly replicates in the host and spreads to susceptible animals by contact or aerosol. Because of the highly infectious nature of FMD, countries free of the disease maintain rigid quarantine and import restrictions on animals and animal products from infected countries in order to prevent its introduction and to allow continued active participation in international trade. The disease does not occur in the U.S., Canada, or Mexico, and its continued absence from North America is a priority for the U.S. livestock industry and the United States Department of Agriculture (USDA).
The virus that causes FMD (FMDV) is an RNA virus classified as a member of the genus Aphthovirus and the family Picornaviridae (see Cooper et al., Intervirology, 10: 165-180 (1978)). There are seven known serotypes of FMDV: the European serotypes A, O and C, the South Africa Territories serotypes SAT 1, SAT 2, and SAT 3, and the Asia 1 serotype. A number of antigenically distinct subtypes are recognized within each of these serotypes. Indeed, for each serotype or subtype several genetically distinct variants exist.
Disease incidence in previously FMD-free countries, such as the United Kingdom in 2001 (see, e.g. Knowles et al., Vet. Rec., 148: 258-259 (2001)) are controlled by inhibition of susceptible animal movement, slaughter of infected and in-contact animals, and decontamination. Inactivated whole virus vaccines are conventionally used in FMD control programs as a last resort mainly because of the adverse economic affects of vaccination as compared to slaughter, despite their success in controlling the disease. Other problems associated with the currently available FMD vaccine include a requirement for high-containment facilities to produce the virus needed for vaccine manufacture, the antigenic variation of the virus resulting in numerous virus serotypes and subtypes, and the inability of vaccines to rapidly induce protective immunity.
To circumvent these problems, researchers have explored using viral vectors as FMD vaccines. For example, E1-deficient adenoviral vectors have been engineered to encode the FMD virus (FMDV) empty capsid and the 3C protease (Pacheco et al., Virology, 337: 205-209 (2005)), as well as interferons (U.S. Patent Application Publication 2003/0171314 A1). Such adenoviral vectors, however, have not been shown to induce the rapid antibody response required to combat an FMDV outbreak.
Accordingly, there remains a need for viral vector vaccines that elicit a more rapid and complete immune response against foot-and-mouth disease. The invention provides such viral vectors.